Methyl iodide → 6-[4-(4-Fluorobenzoyl)piperidin-1-YL]pyridazine-3-carboxylic acid (2-cyclopropylethyl)methylamide

HRID 552169

Reaktionsgleichung

Reaktionsgleichung von HRID 552169
[CH:1]1([CH2:4][CH2:5][NH:6][C:7]([C:9]2[N:10]=[N:11][C:12]([N:15]3[CH2:20][CH2:19][CH:18]([C:21](=[O:29])[C:22]4[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=4)[CH2:17][CH2:16]3)=[CH:13][CH:14]=2)=[O:8])[CH2:3][CH2:2]1.[H-].[Na+].[CH3:32]I>C1COCC1>[CH:1]1([CH2:4][CH2:5][N:6]([CH3:32])[C:7]([C:9]2[N:10]=[N:11][C:12]([N:15]3[CH2:16][CH2:17][CH:18]([C:21](=[O:29])[C:22]4[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=4)[CH2:19][CH2:20]3)=[CH:13][CH:14]=2)=[O:8])[CH2:2][CH2:3]1

Komponenten

5

Edukt 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 116253966-[4-(4-Fluorobenzoyl)piperidin-1-YL]pyridazine-3-carboxylic acid (2-cyclopropylethyl)amide

Produkt 1

HCID 115460356-[4-(4-Fluorobenzoyl)piperidin-1-YL]pyridazine-3-carboxylic acid (2-cyclopropylethyl)methylamideAusbeute 52 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a mixture of 6-[4-(4-fluorobenzoyl)piperidin-1-yl]pyridazine-3-carboxylic acid (2-cyclopropylethyl)amide (0.075 g, 0.189 mmol) and sodium hydride (0.009 g, 60% in mineral oil) in THF (15 mL) was added methyl iodide (0.134 g, 0.945 mmol) at 0° C. The reaction mixture was stirred at ambient temperature overnight, then concentrated in vacuo. The residue was diluted with water and then extracted with ethyl acetate. The organic layer was dried, concentrated and purified by column chromatography to yield the title compound in 52% yield (0.040 g). 1H NMR (300 MHz, CDCl3) δ 8.0-7.96 (m, 2H), 7.69-7.6 (m, 1H), 7.18-7.07 (m, 2H), 6.98-6.94 (m, 1H), 5.54-4.45 (m, 2H), 3.8-3.73 (m, 1H), 3.65-3.47 (m, 2H), 3.32-3.07 (m, 4H), 2.06-1.7 (m, 5H), 1.6-1.47 (m, 2H), 0.79-0.67 (m, 1H), 0.52-0.41 (m, 1H), 0.36-0.28 (m, 1H), 0.12-0.07 (m, 1H), 0.1-−0.06 (m, 1H). 13C NMR (75 MHz, CDCl3) δ 200.1, 167.5, 167.2, 166.3, 164.1, 158.8, 148.6, 148.5, 132.1, 132.07, 131.0, 130.9, 129.2, 128.9, 116.1, 115.8, 112.3, 112.2, 51.6, 49.2, 44.5, 43.2, 38.2, 34.4, 33.6, 32.0, 27.9, 8.6, 8.3, 4.3, 4.26. MS (ES+) m/z 411 (M+1).

Aufarbeitung

  1. concentrationconcentrated in vacuo
  2. additionThe residue was diluted with water
  3. extractionextracted with ethyl acetate
  4. customThe organic layer was dried
  5. concentrationconcentrated
  6. custompurified by column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-0568e4230d1a49a0bfed37a5680f7c43
Quelldatensatz
uspto-grants-2011_05
Patentnummer
US07951805B2

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